Prime-boost vaccination with recombinant protein and adenovirus-vectored expressing Plasmodium vivax circumsporozoite protein (CSP) partially protects mice against a Pb/Pv sporozoite challenge

Background Vaccine development against Plasmodium vivax malaria lags behind that for Plasmodium falciparum. Toward that goal, we have performed studies in mice using recombinant antigens based on P. vivax circumsporozoite protein (CSP). Materials and Methods We expressed two novel chimeric proteins in P. pastoris by merging central repeat regions of CSP alleles (VK210, VK247, and P. vivax-like) flanked by N- and C-terminal regions (yPvCSP-AllFL) or C-terminal only (yPvCSP-AllCT). We also generated replicationdefective adenovirus vectors expressing CSP of human serotype 5 (AdHu5) and chimpanzee serotype 68 (AdC68). Mice were vaccinated with three doses of yPvCSP in Poly (I:C) adjuvant, or with a regimen of adenovirus immunization followed by two immunizations with yPvCSP. Results and Conclusions Mice immunized with yPvCSP generated high IgG titres specific to all CSP alleles (>105) and no differences were observed among them. There was a significant predominance of IgG1 (P < 0.001) against PvCSP-VK210 and P. vivax-like. After challenge with P. berghei ANKA transgenic parasites expressing Pb/PvVK210 or Pb/PvVK247 , significant time delays for parasitemia were observed in all vaccinated mice (P<0.0001) than in the control group. These vaccine formulations should be clinically tried for their potential as protective universal vaccine against P. vivax malaria. Financing: CNPq 204487/2014-5 150163/2016-9, FAPESP 2012/13032-5, PNPD/CAPES, INCTV, Wellcome Trust.